Valacyclovir hydrochloride Chemical Properties

Melting point:

170-172°C

storage temp. 

Keep in dark place,Sealed in dry,Store in freezer, under -20°C

solubility 

H2O: >20mg/mL

form 

solid

color 

white

Water Solubility 

H2O: >20mg/mL

λmax

253nm(H2O)(lit.)

Merck 

14,9899

Stability:

Hygroscopic

InChI

InChI=1/C13H20N6O4.ClH/c1-7(2)8(14)12(21)23-4-3-22-6-19-5-16-9-10(19)17-13(15)18-11(9)20;/h5,7-8H,3-4,6,14H2,1-2H3,(H3,15,17,18,20);1H/t8-;/s3

InChIKey

ZCDDBUOENGJMLV-JNODIIHCNA-N

SMILES

C(N1C=NC2C(N=C(NC=21)N)=O)OCCOC(=O)[C@@H](N)C(C)C.Cl |&1:18,r|

CAS DataBase Reference

124832-27-5(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-22

Safety Statements 

26-36-24/25

RIDADR 

3077

WGK Germany 

3

HS Code 

29335990

Valacyclovir hydrochloride Usage And Synthesis

Description

Valacyclovir hydrochloride, an orally active L-valyl ester of the potent antiviral agent aciclovir, was launched in 1995 in the United Kingdom for the treatment of herpes simplex virus (HSV) infections of the skin and mucous membranes, including initial and recurrent genital herpes. As a prodrug, valaciclovir has an improved pharmacokinetic profile to aciclovir. It is rapidly absorbed after oral administration and extensively converted to aciclovir via first-pass metabolism to achieve plasma levels of aciclovir comparable to those seen with aciclovir via i.v. route. Valacyclovir is then activated selectively in virus-infected cells by viral thymidine kinase to form aciclovir triphosphate in a stepwise fashion. This active species inhibits viral DNA polymerase via irreversible binding to the active site of the enzyme. Once aciclovir is incorporated into the elongating viral DNA, it terminates replication of the viral DNA strand, an antiviral mechanism unique to aciclovir. Valacyclovir is reportedly in clinical trials for the suppression of cytomegalovirus infection and disease in renal transplant patients.

Chemical Properties

White Crystalline Powder

Originator

Glaxo Wellcome (United Kingdom)

History

Valacyclovir hydrochloride is an antiviral drug developed by GlaxoSmithKline and marketed under the brand name Valtrex. It was first approved by the FDA in June 2001 for the treatment of infections caused by the herpes simplex virus (HSV), including genital herpes, cold sores, and shingles in adults, as well as cold sores in children.

Uses

Acyclovir (A192400) impurity. The L-Valine ester prodrug of Acyclovir.

Uses

Valaciclovir hydrochloride is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B.

Definition

ChEBI: Valacyclovir hydrochloride is an organic molecular entity.

brand name

Valtrex (GlaxoSmithKline).

General Description

Valacyclovir (Valtrex) is the hydrochloride salt of the Lvalylester of acyclovir. The compound is a water-solublecrystalline solid, and it is a prodrug intended to increase thebioavailability of acyclovir by increasing lipophilicity.Valacyclovir is hydrolyzed rapidly and almost completely toacyclovir following oral administration.
Valacyclovir has been approved for the treatment of herpeszoster (shingles) in immunocompromised patients. Theside effect profile observed in valacyclovir is comparablewith bioequivalent doses of acyclovir.

Pharmacokinetics

The binding of valacyclovir to human plasma proteins ranges between 13.5 to 17.9%. The plasma elimination half-life of acyclovir is 2.5 to 3.3 hours. The bioavailability of valacyclovir hydrochloride is 54%, compared to approximately 20% for oral acyclovir, and it is as effective as acyclovir in decreasing the duration of pain associated with posttherapeutic neuralgia and episodes of genital lesion healing.

Side effects

The adverse effects are similar to acyclovir, which include nausea, headache, vomiting, constipation, and anorexia.

Synthesis

General procedure: To a 1L hydrogenation kettle was added (S)-2-((2-amino-6-oxo-1H-purin-9(6H)-yl)methoxy)ethyl 2-(((benzyloxy)carbonyl)amino)-3-methylbutanoate (50g), concentrated hydrochloric acid (9.6mL), 5% palladium-carbon catalyst (5g) and water (350mL), and the reaction was carried out for 6 to 12 hours under the conditions of hydrogen pressure of 3kg/cm2 and temperature of 25-30°C. -30°C for 6 to 12 hours. Upon completion of the reaction, the reaction mixture was vacuum filtered and the filter cake was washed with water. The filtrate was concentrated under reduced pressure and subsequently cooled to room temperature. Isopropanol was added to the concentrate, which was further cooled to 5-10 °C and maintained at that temperature for 1 hour. The precipitated solid was (S)-2-((2-amino-6-oxo-1H-purin-9(6H)-yl)methoxy)ethyl 2-amino-3-methylbutyrate hydrochloride, which was filtered and washed with cold isopropanol to give the product. The yield was 92% and the purity was 99.8%. Analytical conditions: Chromatographic column: USP L1, 4.6×150 mm, 3.5 μm (Zorbax SB-C18, item 863953-914) Detector: UV 250nm Mobile phase A: In a 1000mL volumetric flask, add 2.8mL triethylamine with 800mL ultrapure water, adjust pH to 5.00±0.05 with glacial acetic acid, and settle to scale. Mobile phase B: acetonitrile Injection volume: 50μL Column temperature: 30°C Flow rate: 1.0mL/min Gradient elution

References

[1] Asian Journal of Chemistry, 2010, vol. 22, # 5, p. 4092 - 4098
[2] Patent: WO2013/76688, 2013, A1. Location in patent: Page/Page column 10-11
[3] Patent: US2014/296520, 2014, A1. Location in patent: Paragraph 0043
[4] Journal of Pharmaceutical Sciences, 2001, vol. 90, # 10, p. 1505 - 1515
[5] Patent: WO2006/35452, 2006, A1. Location in patent: Page/Page column 5-6

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